Recommendations for Prevention and Control of Influenza in Children, 2022–2023

This technical report accompanies the recommendations of the American Academy of Pediatrics (AAP) for the routine use of influenza vaccine and antiviral medications in the prevention and treatment of influenza in children during the 2022 to 2023 season.¹ 

Recent influenza seasons in the United States have varied by severity, duration, and impact on children’s health (Table 1). Influenza vaccine effectiveness has likewise varied by year, influenza type, and influenza A virus subtype, and age group of the child immunized (Fig 1).

After a substantially and unusually mild 2020 to 2021 influenza season, likely because of the circulation of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) and the implementation of pandemic mitigation measures, public health experts predicted that the 2021 to 2022 influenza season could be early and severe because of reduced population immunity resulting from minimal influenza virus circulation since March 2020. Interim reports of influenza activity did not confirm that prediction. Between October 1, 2021, and June 11, 2022, the Centers for Disease Control and Prevention (CDC) estimated the burden of influenza to include 8 000 000 to 13 000 000 illnesses and 82 000 to 170 000 hospitalizations (https://www.cdc.gov/flu/about/burden/preliminary-in-season-estimates.htm). The cumulative hospitalization rate of 17.3 of 100 000 was higher than the rate for the 2020 to 2021 season but lower that the rate observed during the 8 seasons preceding the coronavirus disease 2019 (COVID-19) pandemic. Among people younger than 65 years, hospitalization rates were highest among children 0 to 4 years of age (21.8 of 100 000). In a sample of hospitalized children reported to the Influenza Hospital Surveillance Network (FluSurv-NET), 64.5% had at least 1 underlying medical condition, the most common of which was asthma (https://gis.cdc.gov/grasp/fluview/FluHospChars.html). The CDC estimated influenza-related deaths to be between 5000 and 14 000; 33 deaths were reported in children through June 11, 2022 (Fig 2).

Through July 2, 2022, more than 97% of the influenza viruses identified were A (H3N2). In an interim analysis, most were antigenically distinct from the vaccine reference virus.²  Information about influenza surveillance is available through the CDC Voice Information System (1-800-232-4636) and is posted weekly on the CDC Web site (www.cdc.gov/flu/index.htm).

In a typical influenza season, the disease burden among children is substantial. Each year, an estimated 9% of United States children develop symptomatic influenza virus infection, and hospitalization rates of children are highest in those younger than 5 years.^3,4  Deaths from influenza occur in children with and without other underlying medical conditions.⁵  Over 9 influenza seasons in the United States following the 2009 H1N1 pandemic, adjusted influenza-associated hospitalization incidence rates ranged from 10 to 375 per 100 000 persons <18 years of age each season; rates were highest among infants <6 months of age and decreased with increasing age.⁶  In this cross-sectional study that included data from 14 US Influenza Hospitalization Surveillance Network sites, 13 235 children were hospitalized, and of these, 2676 (20%) were admitted to the ICU, 2262 (17%) had pneumonia, and 690 (5%) required mechanical ventilation. Seventy-two children (0.5%) died during hospitalization. In multivariable models, the odds of severe outcomes, including in-hospital death, were highest in children 13 to 17 years of age.

In another cross-sectional study that included 10 influenza seasons, higher rates of severe influenza disease were reported in Black, Hispanic, American Indian or Alaska Native, and Asian or Pacific Islander people compared with white people, and differences were pronounced in children ≤4 years of age.⁷  In this age group, hospitalization rates were higher in Black children (relative risk [RR]: 2.21; 95% confidence interval [CI]: 2.10 to 2.33), Hispanic children (RR: 1.87; 95% CI: 1.77 to 1.97), American Indian or Alaska Native children (RR: 3.00; 95% CI: 2.55 to 3.53), and Asian or Pacific Islander children (RR: 1.26; 95% CI: 1.16 to 1.38) compared with white children. Rates of ICU admission were also higher (Black children: RR: 2.74; 95% CI: 2.43 to 3.09; Hispanic children: RR: 1.96; 95% CI: 1.73 to 2.23; American Indian or Alaska Native children: RR: 3.51; 95% CI: 2.45 to 5.05). The rate of in-hospital death was 3- to 4-fold higher in Black, Hispanic, and Asian or Pacific Islander children compared with white children. Importantly, factors associated with disparities observed with other respiratory viruses (eg, SARS-CoV-2 and respiratory syncytial virus), including lack of access to quality health care, crowded living conditions, and social vulnerability, were not evaluated in this study.^8,9 

Although clinicians are familiar with respiratory complications of influenza, including pneumonia, respiratory distress syndrome, and respiratory failure, other complications may occur. ∼ 8% to 11% of hospitalized children experience neurologic complications, and these are more frequent in children with underlying neurologic conditions.^10,11  In a multicenter, cross-sectional study of 22 676 children 2 to 17 years of age hospitalized with influenza between 2015 and 2020, 7.6% had a neurologic complication, of which febrile seizures (1477; 5%), encephalopathy (514; 1.7%), and nonfebrile seizures (364; 1.2%) were the most common. Male sex (adjusted odds ratio [aOR]: 1.1; 95% CI: 1.02 to 1.21), Asian race or ethnicity (aOR: 1.7; 95% CI: 1.4 to 2.1) (compared with non-Hispanic white), and the presence of a chronic neurologic condition aOR: 3.7; 95% CI: 3.1 to 4.2) were associated with the development of a neurologic complication. In a single-center, historical cohort study of children hospitalized with laboratory-confirmed influenza between 2010 and 2017, 10.8% of children experienced at least 1 neurologic complication. A pre-existing neurologic condition (aOR: 4.6; P <.001), age ≤5 years (aOR: 1.6; P = .17) and lack of a seasonal influenza vaccine (aOR: 1.6; P = .020) were independently associated with the development of a neurologic complication. Protecting all children against influenza through timely vaccination remains critically important.

Children younger than 5 years (especially those younger than 2 years) and children of any age with certain underlying medical conditions have a high risk of complications from influenza (see Table 4 in the policy statement [http://www.pediatrics.org/cgi/doi/10.1542/peds.2022-059275]). In addition, influenza vaccination is particularly important in certain populations with social or community characteristics, resulting in higher rates of hospitalization from influenza and increased vulnerability to COVID-19.^7,12  Increased efforts are needed to eliminate barriers to immunization in all persons experiencing higher rates of adverse outcomes from influenza virus infection.

Although influenza vaccination does not prevent all cases of influenza, it does offer substantial protection against severe and life-threatening disease, as detailed below.

A robust body of evidence supports the effectiveness of influenza vaccination in preventing hospitalization in children, even during seasons in which overall vaccine effectiveness is lower (Table 2).^13–21  According to a systematic review, effectiveness is the highest in children younger than 5 years.¹⁹  Because there was negligible influenza virus circulation during the 2020 to 2021 season, and low influenza activity during 2021 to 2022, assessing the 2019 to 2020 season, the most recent season with substantial influenza virus circulation, is illustrative. During this season, influenza B/Victoria viruses predominated early, followed by influenza A (H1N1)pdm09. More than 95% of circulating influenza B/Victoria viruses were antigenically and genetically distinct from the influenza B/Victoria vaccine strain. Overall, VE for medically attended influenza illness was 39% (Fig 1). Nevertheless, data from the New Vaccine Surveillance Network demonstrated that overall VE for influenza-related hospitalizations was 62% (95% CI: 52% to 71%); VE for B/Victoria viruses was 54% (95% CI: 33% to 69%), and VE for A(H1N1)pdm09 was 64% (95% CI: 49% to 75%).²²  The CDC estimates that influenza vaccination prevented 16% of hospitalizations among children 5 through 17 years of age and 28% among children 6 months through 4 years of age.^23,24 

Historically, up to 80% of influenza-associated pediatric deaths have occurred in unvaccinated children 6 months and older. Influenza vaccination is associated with reduced risk of laboratory-confirmed influenza-related pediatric death.²¹  In 1 case-cohort analysis comparing vaccination uptake in laboratory-confirmed influenza-associated pediatric deaths with estimated vaccination coverage among pediatric cohorts in the United States from 2010 to 2014, only 26% of children had received vaccine before illness onset, compared with an average vaccination coverage of 48%.²¹  Overall, VE against influenza-associated death in children was 65% (95% CI: 54% to 74%). More than half of children in this study who died of influenza had ≥1 underlying medical condition associated with increased risk of severe influenza-related complications; only 1 in 3 of these at-risk children had been vaccinated, yet VE against death in children with underlying conditions was 51% (95% CI: 31% to 67%). Similarly, influenza vaccination reduces by three quarters the risk of severe, life-threatening laboratory-confirmed influenza in children requiring admission to the ICU.²⁵  The influenza virus type might also affect the severity of disease. In a study of hospitalizations for influenza A versus B, the odds of mortality were significantly greater with influenza B than with influenza A and not entirely explained by underlying health conditions.²⁶ 

The seasonal influenza vaccines licensed for children and adults for the 2022 to 2023 season are described in Table 2 in the policy statement (http://www.pediatrics.org/cgi/doi/10.1542/peds.2022-059275). More than one product may be appropriate for a given patient, and vaccination should not be delayed to obtain a specific product. All 2022 to 2023 seasonal influenza vaccines are quadrivalent and contain the same influenza strains as recommended by the World Health Organization and the US Food and Drug Administration (FDA)’s Vaccines and Related Biological Products Advisory Committee for the Northern Hemisphere (see Table 1 in the policy statement [http://www.pediatrics.org/cgi/doi/10.1542/peds.2022-059275]).^27,28  The influenza A(H3N2) and influenza B Victoria lineage vaccine components are different this season compared with last season, whereas the influenza A (H1N1) and influenza B Yamagata lineage components are unchanged. Different but antigenically related influenza A strains are included in this season’s egg-based and cell-based or recombinant vaccines. However, they are still matched to the strains expected to circulate in the 2022 to 2023 season.

For the 2022 to 2023 season, all licensed inactivated influenza vaccines (IIVs) for children and adults in the United States continue to be quadrivalent, with specific age indications for available formulations (see Table 2 in the policy statement [http://www.pediatrics.org/cgi/doi/10.1542/peds.2022-059275]). Among vaccines available for children, 4 are egg-based (seed strains grown in eggs), and 1 is cell culture-based (seed strains grown in Madin-Darby canine kidney cells). All inactivated egg-based vaccines (Afluria Quadrivalent, Fluarix Quadrivalent, FluLaval Quadrivalent, and Fluzone Quadrivalent) are licensed for children 6 months and older, and most are available in single-dose, thimerosal-free, prefilled syringes. The only pediatric cell culture-based vaccine (Flucelvax Quadrivalent) is now licensed for children 6 months and older.²⁹  The minimum age indication was lowered from 4 years to 2 years of age in March 2021 on the basis of data from a randomized, double-blind clinical efficacy study conducted among children 2 to 18 years of age over 3 seasons (2017 in the Southern Hemisphere and 2017 to 2018 and 2018 to 2019 in the Northern Hemisphere), in which Flucelvax Quadrivalent demonstrated efficacy against laboratory-confirmed influenza illness of 54.6% (95% CI: 45.7% to 62.1%), compared with a control vaccine (meningococcal serogroup ACWY conjugate vaccine).³⁰  Subsequently, the FDA approved an expansion in age indication from 2 years and older to 6 months and older for Flucelvax Quadrivalent on October 14, 2021.³¹ 

A quadrivalent recombinant baculovirus-expressed hemagglutinin influenza vaccine (quadrivalent recombinant influenza vaccine [RIV4] [Flublok Quadrivalent]) is licensed only for people 18 years and older. A quadrivalent high-dose inactivated influenza vaccine (HD-IIV4 [Fluzone High Dose Quadrivalent]) containing 4 times the amount of antigen for each virus strain compared with the standard dose vaccines is licensed only for people 65 years and older. The quadrivalent MF-59 adjuvanted inactivated vaccine (aIIV4 [Fluad Quadrivalent]) is also licensed for people 65 years and older.²⁹  Vaccine adjuvants may elicit a more robust immune response. In June 2022, the Advisory Committee on Immunization Practices (ACIP) recommended preferential use of a higher dose or adjuvanted influenza vaccine for adults 65 years and older; recommended vaccines include Fluzone High-Dose Quadrivalent, Flublok Quadrivalent, and Fluad Quadrivalent.²⁹  Adjuvanted seasonal influenza vaccines are not licensed for children in the United States; however, studies of adjuvanted vaccines in children are ongoing.^32–35 

Children 6 months and older can receive any licensed, age-appropriate IIV. Quadrivalent egg-based and cell culture-based IIVs contain 15 µg hemagglutinin from each strain in 0.5 mL. The recommended dose volume (and, therefore, the recommended antigen content) for younger children varies by product. The dose of Fluarix Quadrivalent, FluLaval Quadrivalent, and Flucelvax Quadrivalent, is 0.5 mL for all children 6 months of age and older.^30,36–38  Children 6 through 35 months of age can receive a 0.25 mL or 0.5 mL dose of Fluzone Quadrivalent.³⁹  These 2 formulations demonstrated comparable safety and immunogenicity in a single, randomized multicenter study.⁴⁰  The Fluzone Quadrivalent 0.25 mL prefilled syringe is no longer available, but the smaller dose can be withdrawn from a single or multidose vial. Children 3 years and older should receive 0.5 mL. Afluria Quadrivalent has a 0.25 mL presentation for children 6 through 35 months of age and a 0.5-mL product for children 3 years and older only.⁴¹  However, the 0.25-mL prefilled syringes are not expected to be available for the 2022–2023 season. For children aged 6 through 35 months, a 0.25-mL dose must be obtained from a multidose vial.

The AAP supports the current World Health Organization recommendations for use of thimerosal as a preservative in multiuse vials in the global vaccine supply.⁴²  Thimerosal-containing vaccines are not associated with an increased risk of autism spectrum disorder in children. Thimerosal from vaccines has not been linked to any neurologic condition. Despite the lack of evidence of harm, some states have legislation restricting the use of vaccines that contain even trace amounts of thimerosal. The benefits of protecting children against the known risks of influenza are clear. Therefore, to the extent permitted by state law, children should receive any available formulation of IIV rather than delaying vaccination while waiting for reduced thimerosal-content or thimerosal-free vaccines. IIV formulations that are free of even trace amounts of thimerosal are widely available, as described in Table 2 in the policy statement (http://www.pediatrics.org/cgi/doi/10.1542/peds.2022-059275). Additional information to assist clinicians in responding to parental concerns about thimerosal are available at https://www.cdc.gov/vaccinesafety/concerns/thimerosal/index.html.

The CDC has published Best Practice Guidelines (https://www.cdc.gov/vaccines/pandemic-guidance/index.html) for vaccine storage and administration. Additionally, guidance from the AAP details the components of a written disaster plan, including a comprehensive vaccine management protocol to keep the vaccine storage temperature constant during a power failure or other disaster (see PedPreparednessKit.pdf [aap.org]).

IIVs for intramuscular (IM) injection are shipped and stored at 2°C to 8°C (36°F to 46°F); vaccines that are inadvertently frozen should not be used. Vaccines are administered intramuscularly into the anterolateral thigh of infants and young children and into the deltoid muscle of older children and adults. Given that various IIV formulations are available, careful attention should be paid to ensure that each product is used according to its approved age indication, dosing, and volume of administration (see Table 2 in the policy statement [http://www.pediatrics.org/cgi/doi/10.1542/peds.2022-059275]). In each instance, the recommended volume may be administered from an appropriate prefilled syringe, single-dose vial, or multidose vial, as supplied by the manufacturer. Importantly, dose volume is different from the number of doses needed to complete vaccination. For vaccines that include a multidose vial presentation, the maximum number of doses drawn from a multidose vial is specified in the package insert and should not be exceeded; residual product must be discarded, regardless of the remaining volume in the vial. A 0.5 mL unit dose of any IIV should not be split into 2 separate 0.25 mL doses.

Recommendations for concomitant administration of influenza vaccine and other vaccines is detailed in the policy statement. Influenza vaccine can be administered concomitantly or at any time before or after administration of the currently available COVID-19 vaccines. In 1 multicenter, randomized phase 4 trial of 679 adults in the United Kingdom, concomitant administration of an age-appropriate influenza vaccine and a COVID-19 vaccine (either ChAdOx1 or BNT162b2) was safe and did not adversely affect immune responses.⁴³  Of note, ChAdOx1 is not authorized for use in the United States. A phase 2, randomized, open label study of US adults 65 years or older who received concomitant administration of a high-dose quadrivalent influenza vaccine and an mRNA-1273 COVID-19 vaccine reported similar results.⁴⁴  A randomized study evaluating the safety of simultaneous versus sequential administration of quadrivalent inactivated influenza vaccine and mRNA COVID-19 vaccine adults and adolescents 12 years and older is ongoing (https://clinicaltrials.gov/ct2/show/NCT05028361?term=Influenza±vaccine%2C±children&cond=covid-19±vaccine&draw= 2&rank=1).

Although clinical trial data are not available for concomitant administration of COVID-19 vaccine with other vaccines in children, including influenza vaccine, extensive experience with non-COVID-19 vaccines has demonstrated that immunogenicity and adverse event profiles are generally similar when vaccines are administered simultaneously as when they are administered alone.^45–49  Providers are encouraged to consult the most current guidance from the AAP and the CDC ACIP regarding coadministration of COVID-19 vaccines with other vaccines.⁵⁰  Overall, the benefits of timely vaccination with same-day administration of IIV and other recommended vaccines outweigh the risk of potential reactogenicity in children.

IIVs are well tolerated in children and can be used in healthy children as well as those with underlying chronic medical conditions. The most common injection site adverse reactions following administration of IIV in children are injection site pain (17% to 67%), redness (10% to 37%), and swelling 13% to 25%). The most common systemic adverse events are drowsiness (13% to 38%), irritability (16% to 54%), loss of appetite (14% to 32%), fatigue (17% to 20%), muscle aches (10% to 39%), headache (10% to 23%), arthralgia (10% to 13%), and gastrointestinal tract symptoms (10% to 20%).

The intranasal live attenuated influenza vaccine (LAIV) was initially licensed in the United States in 2003 for people 5 through 49 years of age as a trivalent formulation (LAIV3), and the approved age group was extended to 2 years of age in 2007. The quadrivalent formulation (LAIV4) licensed in 2012 was first available during the 2013 to 2014 influenza season, replacing LAIV3. The history of LAIV use in the United States, along with a detailed discussion of vaccine efficacy over serial seasons, is available in the 2021 technical report.⁵¹ 

The cold-adapted, temperature-sensitive LAIV4 formulation is shipped and stored at 2°C to 8°C (35°F to 46°F). It is administered intranasally in a prefilled, single-use sprayer containing 0.2 mL of vaccine. A removable dose-divider clip is attached to the sprayer to facilitate administration of 0.1 mL separately into each nostril. If the child sneezes immediately after administration, the dose should not be repeated. Administration of LAIV intranasally is not an aerosol-generating procedure; however, vaccine administrators are advised to wear gloves when administering LAIV given the potential for contact with respiratory secretions.

LAIV4 may be administered simultaneously with other inactivated or live vaccines. If not given simultaneously, it is recommended that administration of other nonoral live vaccines is separated by a 4 week interval from LAIV4 vaccination. The most commonly reported reactions of LAIV4 in children are runny nose or nasal congestion (20% to 75%), headache (2% to 46%), fever (up to 26%), vomiting (3% to 13%), abdominal pain (2%) and myalgias (up to 21%).

IIV (or RIV if age-eligible) is the vaccine of choice for anyone in close contact with a subset of severely immunocompromised people (ie, those requiring a protected environment). This preference is based on the theoretical risk of infection attributable to an LAIV strain in an immunocompromised contact of an LAIV-immunized person. Health care personnel (HCP) immunized with LAIV may continue to work in most units of a hospital, including the NICU and general oncology ward, using standard infection control techniques. As a precautionary measure, people recently vaccinated with LAIV should restrict contact with severely immunocompromised patients (eg, those requiring a protective environment) for 7 days after vaccination, although there have been no reports of LAIV transmission from a vaccinated person to an immunocompromised person. In the theoretical scenario in which an immunocompromised host develops a symptomatic LAIV infection, the LAIV strains are susceptible to antiviral medications.

Although peak influenza activity in the United States typically occurs from January through March, influenza viruses can circulate from early fall (October) to late spring (May), with 1 or more disease peaks. This pattern of circulation was substantially altered during the COVID-19 pandemic. Predicting the onset and duration or the severity of the influenza season with accuracy is impossible.

Timely influenza vaccination is important to ensure that individuals are optimally protected before influenza viruses are circulating in the community. Thus, the AAP and CDC recommend children, especially those who need 2 doses, should be immunized as soon as vaccine becomes available and complete influenza vaccination by the end of October. Because the duration of the influenza season is unpredictable, practices should continue to vaccinate individuals as long as influenza viruses are circulating and unexpired vaccine is available.

Immunity after influenza vaccination can wane over time.⁵²  Studies in adults suggest that very early vaccination (July or August) might be associated with suboptimal immunity before the end of the influenza season, and the CDC now discourages influenza vaccination in the summer months for most adults.²⁹  The data are less definitive in children. In some studies, vaccine effectiveness (VE) decreased within a single influenza season, and this decrease correlated with increasing time after vaccination. However, this decay in VE was not consistent across different age groups and varied by season and virus types and influenza A virus subtypes.^53–61  Waning VE was more evident among older adults and younger children^54,56  and with influenza A(H3N2) viruses more than influenza A(H1N1) or B viruses.^55,57,60  A multiseason analysis from the US Flu VE Network found that VE declined by approximately 7% per month for influenza A (H3N2) and influenza B and by 6% to 11% per month for influenza A (H1N1)pdm09 in individuals 9 years and older.⁵³  VE remained greater than 0 for at least 5 to 6 months after vaccination. A more recent study including children older than 2 years also found evidence of declining VE with an odds ratio increasing approximately 16% with each additional 28 days from vaccine administration.⁵⁹  Another study evaluating VE in both adults and children from the 2011 to 2012 through the 2013 to 2014 influenza seasons demonstrated 54% to 67% protection from 0 to 180 days after vaccination.⁵⁷  A single center study of 3595 children during the 2017 to 2018 season demonstrated an overall VE of 52% with no evidence of waning immunity in children up to 183 days after vaccination (median, 81 [interquartile range, 52–111] days), although the study may have been underpowered for this outcome.⁶² 

Collectively, these studies support the current recommendation to immunize children as soon as possible after vaccine becomes available. An early onset of the influenza season is a concern when considering delaying vaccination, and delays increase the likelihood of missing influenza vaccination altogether.²⁹ 

Although influenza activity in the United States is typically low during the summer, influenza cases and outbreaks can occur, particularly among international travelers, who may be exposed to influenza year-round, depending on destination. Individuals who did not receive the current seasonal influenza vaccine and who are traveling to parts of the world where influenza activity is ongoing should consider influenza vaccination ≥2 weeks before departure, if available.⁶³ 

Contraindications and precautions to available influenza vaccines are detailed in Table 5 in the policy statement (http://www.pediatrics.org/cgi/doi/10.1542/peds.2022-059275). A precaution for vaccination is a condition that might increase the risk or seriousness of a vaccine-related adverse reaction. A precaution also may exist for conditions that might compromise the ability of the host to develop immunity after vaccination. Vaccination may be recommended in the presence of a precaution if the benefit of protection from the vaccine outweighs the potential risks.

Although a severe allergic reaction (eg, anaphylaxis) to a previous dose of any influenza vaccine is generally a contraindication to future receipt of influenza vaccines, the AAP recommends that children who have had an allergic reaction after a previous dose of any influenza vaccine be evaluated by an allergist to determine whether future receipt of the vaccine is appropriate. Children who are allergic to gelatin (very rare) should receive IIV (or RIV if age eligible) instead of LAIV.

Mild illnesses, with or without fever, are not contraindications to the use of influenza vaccines, including among children with mild upper respiratory infection symptoms or allergic rhinitis. In children judged by the clinician to have a moderate to severe illness, vaccination should be deferred until resolution of the illness. Children with confirmed COVID-19 are generally advised to defer visits for routine vaccination, including influenza vaccination, until criteria (https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html) have been met for them to discontinue isolation and until they are no longer moderately to severely ill (https://www.cdc.gov/vaccines/pandemic-guidance/index.html). However, if they are already in a health care setting and their illness is mild, they can receive influenza vaccine. Children with an amount of nasal congestion that would notably impede vaccine delivery into the nasopharyngeal mucosa may receive IIV or should have LAIV deferred until resolution.

History of Guillain-Barré syndrome (GBS) following influenza vaccine is considered a precaution for the administration of influenza vaccines. GBS is rare, especially in children, and there is a lack of evidence on risk of GBS following influenza vaccination in children. Nonetheless, regardless of age, a history of GBS less than 6 weeks after a previous dose of influenza vaccine is a precaution for administration of influenza vaccine. GBS may occur after influenza virus infection. The benefits of influenza vaccination might outweigh the risks for certain people who have a history of GBS (particularly if not associated with prior influenza vaccination) and who also are at high risk for severe complications from influenza.

There is strong evidence that egg-allergic individuals can safely receive influenza vaccine without any additional precautions beyond those recommended for any vaccine.^64,65  The presence of egg allergy in an individual is not a contraindication to receive IIV or LAIV. Vaccine recipients with egg allergy are at no greater risk for a systemic allergic reaction than those without egg allergy. Therefore, precautions such as choice of a particular vaccine, special observation periods, or restriction of administration to particular medical settings are not warranted and constitute an unnecessary barrier to vaccination. It is not necessary to inquire about egg allergy before the administration of any influenza vaccine, including on screening forms. Routine prevaccination questions regarding anaphylaxis after receipt of any vaccine are appropriate. Standard vaccination practice for all vaccines in children should include the ability to respond to rare acute hypersensitivity reactions. Children who have had a previous allergic reaction to the influenza vaccine should be evaluated by an allergist to determine whether future receipt of the vaccine is appropriate.

Influenza vaccination is recommended by the ACIP, the American College of Obstetrics and Gynecology, and the American Academy of Family Physicians for all pregnant individuals, during any trimester of gestation, to protect against influenza and its complications.^29,66  Substantial evidence has accumulated regarding the efficacy of maternal influenza vaccination in preventing laboratory-confirmed influenza disease and its complications in both mothers and their infants in the first months of life (up to 6 months) through transplacental passage of antibodies.^66–76  Infants born to persons who receive influenza vaccine during pregnancy have been shown to have a risk reduction of up to 72% (95% CI: 39% to 87%) for laboratory-confirmed influenza hospitalization in the first few months of life.⁷⁶ 

Any licensed, recommended, and age-appropriate inactivated influenza vaccine may be administered to pregnant individuals during any trimester of gestation and postpartum, although experience with the use of RIV4 in pregnant individuals is limited. LAIV is contraindicated during pregnancy. Data on the safety of influenza vaccination at any time during pregnancy continues to support the safety of influenza immunization during pregnancy.^{66,68–73,77}  Large retrospective cohort studies that collectively involved more than 80 000 pregnancies, as well as a systematic review and meta-analysis of studies, found no association between influenza vaccine in any trimester and major congenital malformations.^78–80  Assessments of any association with influenza vaccination and preterm birth and small-for-gestational-age infants have yielded inconsistent results, with most studies reporting a protective effect or no association with these outcomes.^81,82  A cohort study from the Vaccines and Medications in Pregnancy Surveillance System (VAMPSS) during the 2010 to 2011 through 2013 to 2014 influenza seasons found no significant association of spontaneous abortion with influenza vaccination in the first trimester or within the first 20 weeks of gestation.⁸³  One observational Vaccine Safety Datalink study conducted during the 2010 to 2011 and 2011 to 2012 influenza seasons indicated an association between receipt of IIV containing H1N1pdm09 and risk of spontaneous abortion, when an H1N1pdm09-containing vaccine had also been received the previous season.⁸⁴  A follow-up study conducted by the same investigators with a larger population and stricter outcome measures did not show this association and further supported the safety of influenza vaccination during pregnancy.⁸⁵ 

Despite clear evidence of benefit to pregnant individuals and their infants, influenza vaccination in this population remains below target levels.⁸⁶  Among those pregnant anytime between October 2020 and January 2021, only 54.5% reported receiving a dose of influenza vaccine since July 1, 2020. During the 2021 to 2022 influenza season, 51.8% of pregnant individuals were vaccinated through April 16, 2022 (https://www.cdc.gov/flu/fluvaxview/dashboard/vaccination- coverage-pregnant.html). Racial disparities exist in maternal uptake of influenza vaccine during pregnancy, with Black women consistently having the lowest rates.⁸⁷  Black women report a lower rate of being offered or recommended to receive influenza vaccine, despite evidence that a provider recommendation is associated with vaccine acceptance.⁷¹  Lower influenza vaccination coverage also has been reported in Medicaid-insured pregnant women compared with privately insured women and in women residing in rural areas compared with those residing in urban areas.^88,89  Pediatricians who interact with pregnant individuals should recommend influenza vaccination, emphasizing the benefits of vaccination for these women and their infants.

Individuals in the postpartum period who did not receive influenza vaccine during pregnancy should be offered influenza vaccination before hospital discharge. Those who decline the vaccine during hospitalization should be encouraged to discuss influenza vaccination with their obstetrician, family physician, nurse midwife, or other trusted provider. Information about free influenza vaccine clinics should be provided in the preferred language to these individuals, especially those who may experience barriers to preventive care.

Influenza vaccination during breastfeeding is safe for mothers and their infants. Breastfeeding is strongly recommended to protect infants against influenza viruses by activating innate antiviral mechanisms, specifically type-1 interferons. Human milk from mothers vaccinated during the third trimester also contains higher levels of influenza-specific immunoglobulin A (IgA).⁹⁰  Greater exclusivity of breastfeeding in the first 6 months of life decreases the episodes of respiratory illness with fever in infants of vaccinated mothers. For infants born to mothers with confirmed influenza illness at delivery, breastfeeding is encouraged, and guidance on breastfeeding practices is available on the CDC Web site (https://www.cdc.gov/breastfeeding/breastfeeding-special-circumstances/ maternal-or-infant-illnesses/influenza.html and https://www.cdc.gov/flu/professionals/infectioncontrol/peri-post-settings. htm). The mother may pump and feed expressed breastmilk if she or her infant are too sick to breastfeed. If the breastfeeding mother requires antiviral agents, treatment with oral oseltamivir is preferred. The CDC does not recommend use of baloxavir for treatment of pregnant or breastfeeding individuals. There are no available efficacy or safety data in pregnant women, and there are no available data regarding the presence of baloxavir in human milk, the effects on the breastfed infant, or the effects on milk production.

Influenza vaccination coverage had been increasing for children before the 2020 to 2021 season but remained below the Healthy People 2030 target of 70% (Fig 3).⁹¹  During the 2020 to 2021 season, the estimated vaccination coverage with ≥1 dose of influenza vaccine was 58.6% among children 6 months through 17 years of age, a decrease of 5.1 percentage points from the prior season. Vaccination coverage varied significantly by race and ethnicity, with the lowest rates in Black children. This decrease in influenza vaccination coverage mirrors the declines in delivery of other routine pediatric vaccines during the pandemic.^92–95  Influenza immunization coverage has continued to lag during the 2021 to 2022 season. Through April 9, 2022, only 55.3% of children 6 months to 17 years had been vaccinated.⁹⁶  Coverage was 8.1 percentage points lower for non-Hispanic Black children compared with non-Hispanic white children (47.0% vs 55.1%, respectively).

The reasons for low influenza vaccination coverage are likely multifactorial. For some families, logistical barriers, including lack of transportation and altered school and work schedules, may have reduced access to routine medical care.⁹⁷  Other families may have avoided care in medical offices out of fear of contracting SARS-CoV-2.⁹⁸  Pandemic mitigation strategies, including masking and social distancing, as well as decreased influenza activity in the community, could have created a perception of decreased risk from influenza, limiting a sense of urgency for influenza vaccination. It is unclear how hesitancy around COVID-19 vaccination may have impacted hesitancy toward other vaccines, including seasonal influenza vaccine.

Achieving high influenza vaccination coverage of infants, children, and adolescents remains a priority to protect them against influenza disease and its complications. Multifaceted strategies are needed to increase influenza vaccination coverage, especially in vulnerable, high-risk populations.

Annual distribution of influenza vaccine to health care facilities serving children and adolescents should be timely to avoid missed opportunities. Concerted efforts should be made to prioritize delivery to primary care settings, especially when supply is limited or delayed. Efforts also should be made to eliminate discrepancies in influenza vaccine supply between privately insured patients and those eligible for vaccination through the Vaccines for Children (VFC) program. In addition, public and private payers should offer adequate payment for influenza vaccine supply and administration to pediatric populations and should eliminate remaining “patient responsibility” cost barriers to influenza vaccination where they still exist. The AAP has developed guidance for addressing influenza vaccine supply, payment, coding, and liability issues (Influenza - aap.org).

The AAP and CDC recommend influenza vaccination at any visit to the medical home during influenza season. Influenza vaccination in the medical home is ideal, especially for the youngest children. Nevertheless, influenza vaccination should also occur in other health care locations, such as subspecialty practices, urgent care clinics, and emergency departments. Hospitalized patients should be vaccinated before discharge, unless medically contraindicated. Alternate venues, such as schools and pharmacies, could also be used. Administering influenza vaccine in these diverse locations may increase uptake among patients who do not have or cannot readily access their medical home and those at high risk for influenza-related complications.^99,100  A system for reporting influenza vaccine administrations is crucial to ensure adequate communication and maintain accurate patient records across settings. Appropriate documentation should be provided to patients and to the medical home. Regional or state immunization information systems (IISs) should be used and prioritized whenever available. IIS integration with electronic health record systems can enhance data accuracy and up-to-date vaccination status.¹⁰¹ 

Practices should consider a variety of evidence-based strategies to improve influenza vaccination of their patients (see Table 3 in the policy statement [http://www.pediatrics.org/cgi/doi/10.1542/peds.2022-059275]). They could expand practice hours (ie, evenings, weekends) or schedule vaccine-only clinics to increase patient access to influenza vaccine during peak periods. They could send reminder or recall messages notifying families of influenza vaccine availability and providing other key information, such as the child’s vaccination status and where, when, and why the child should receive the vaccine.¹⁰²  A variety of modalities can be used, including telephone, text, letter, e-mail, or messaging via the patient portal. In addition, practices should make vaccine-related information readily available to patients and families (ie, via their practice Web site, social media platform, or educational handout).^103,104  Resources are available at https://www.aap.org/en/news-room/campaigns-and- toolkits/immunizations/.

Furthermore, practices should implement strategies to reduce missed opportunities during patient visits. Practices can standardize their workflow to screen all patients for influenza vaccine eligibility and administer the vaccine to any patient who is due for the vaccine. This workflow could be used at all visit types, including preventive care, acute care, and mental or behavioral health visits. Influenza vaccination opportunities should be captured when patients present for other needed vaccines as well. Practices may identify influenza vaccine champion(s) within their practice to spearhead these efforts. The AAP has created tools to help practices prepare for the influenza season and maximize immunization rates (https://services.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/help-for- pediatricians/preparing-for-flu- season/).

Informatic tools can facilitate influenza vaccination. For example, studies have shown that standing vaccine orders and vaccine prompts in the electronic health record increase influenza vaccine uptake in both inpatient and outpatient settings.^105,106  Audits and performance feedback for providers have also been shown to be effective as part of multimodal interventions.¹⁰⁷ 

Effective influenza vaccine communication with patients and families is crucial. Messaging should be consistent across all members of the care team, including front office staff, medical assistants, nurses, and all provider types (including primary care and subspecialty care providers). Practices should educate their staff and providers about influenza and influenza vaccine-related topics, including the importance of annual vaccination, vaccine effectiveness and safety, the 2 dose requirement for certain children, vaccine contraindications, and common parental concerns. Providers should use evidence-based communication strategies in their conversations with families. These include offering a strong, presumptive influenza vaccine recommendation, bundling their recommendation for influenza vaccine with recommendations for other needed vaccines, and pursuing their initial recommendation when families initially decline the vaccine.¹⁰⁸  Resources regarding effective vaccine communication techniques are available on the AAP Web site at https://services.aap.org/en/news-room/campaigns-and- toolkits/immunizations/.

Practices serving children and adolescents may consider offering influenza vaccine to family members and close contacts.¹⁰⁹  The AAP technical report, “Immunizing Parents and Other Close Family Contacts in the Pediatric Office Setting,” provides medical liability risk management guidance on documenting in a separate record screening, informed consent, and National Vaccine Injury Compensations Program (VICP)-required immunization administration data.¹⁰⁹  Guidance is also provided on ascertaining that immunizing adults is covered by customary pediatric medical liability insurance policies for any adverse events not covered by the VICP. Additional resources are available at https://services.aap.org/en/news-room/campaigns-and-toolkits/immunizations/.

Practices also could partner with community stakeholders, including early childhood learning centers, schools, public health agencies, pharmacies, and other organizations, to optimize influenza vaccine distribution, communication, and administration. For example, practices could help with outreach initiatives, such as influenza vaccine fairs or mobile vaccine vans. They could educate families and community members on the importance of influenza vaccination and addressing common concerns. The AAP has created communication resources to convey key messages and to help the public understand influenza vaccination recommendations on the AAP Web site at Flu Campaign Toolkit (aap.org).

The AAP supports mandatory influenza vaccination programs for HCP in all settings, including outpatient locations. Optimal prevention of influenza in these settings requires that at least 90% of HCP are vaccinated. Estimated influenza vaccination coverage of HCP was only 75.9% during the 2020 to 2021 season, compared with 80.6% in the 2019 to 2020 season.¹¹⁰  Coverage levels were highest among HCP whose employers required vaccination (95.9%). Coverage levels were also higher among HCP working in hospitals (91.6%) compared with those working in outpatient settings (77.3%). Influenza vaccination programs for HCP benefit the health of employees, their patients, and members of the community, especially because HCP frequently come into contact with high-risk patients in their clinical settings. The programs reduce HCP absenteeism and may reduce disruptions in care delivery associated with personnel shortages.¹¹¹  Mandatory influenza vaccination of HCPs is considered ethical, just, and necessary to improve patient safety. For the prevention and control of influenza, HCP must prioritize the health and safety of their patients, honor the requirement of causing no harm, and act as role models for both their patients and colleagues by receiving influenza vaccination annually.

Antiviral agents available for both influenza treatment and chemoprophylaxis in children of all ages can be found in Table 6 in the policy statement (http://www.pediatrics.org/cgi/doi/10.1542/peds.2022-059275) (including doses for preterm infants that have not been evaluated by the FDA) and on the CDC Web site.¹¹²  These include the neuraminidase inhibitors (NAIs: oseltamivir, zanamivir, peramivir) and a selective inhibitor of influenza cap-dependent endonuclease (baloxavir), all of which have activity against influenza A and B viruses.¹¹³ 

Oral oseltamivir (Tamiflu) remains the antiviral drug of choice for the management of illness caused by influenza virus infections. Although more difficult to administer, inhaled zanamivir (Relenza) is an equally acceptable alternative for patients who do not have chronic respiratory disease. Baloxavir marboxil (Xofluza) was approved in 2018 for the early treatment of uncomplicated influenza in outpatients 12 years and older who have been ill for no more than 2 days, and in 2019, the FDA expanded the approval to specifically include persons at high risk for influenza complications.^114,115  This antiviral agent for influenza has a different mechanism of action (cap-endonuclease inhibitor) than NAIs, requires only a single oral dose for treatment of uncomplicated influenza; outcomes are similar to those for NAIs.^116,117  In November 2020, baloxavir was approved by the FDA for single-dose postexposure prophylaxis in people 12 years of age and older after exposure to someone with influenza.^118,119  In August of 2022, the age indication for baloxavir was lowered to 5 years for the treatment of acute uncomplicated influenza in otherwise healthy children who have been symptomatic for no more than 48 hours and for chemoprophylaxis of influenza following contact with someone with influenza. The oral suspension formulation of baloxavir will not be available in the United States for the 2022–2023 influenza season, which will limit use in children who are old enough to receive the drug but weigh less than 20 kg.¹²⁰  Options are limited for children who cannot absorb orally or enterally administered oseltamivir or tolerate inhaled zanamivir. Intravenous peramivir (Rapivab), a third NAI, was approved in September 2017 as treatment of acute uncomplicated influenza in ambulatory children 2 years and older who have been symptomatic for no more than 2 days. In February 2021, the FDA expanded approval to include children as young as 6 months of age. The efficacy of peramivir in patients with serious influenza requiring hospitalization has not been established.¹¹³  IV zanamivir is not approved in the United States and has not been available for compassionate use since the 2017 to 2018 season.¹²¹ 

Randomized controlled trials (RCTs) to evaluate the efficacy of influenza antiviral medications among outpatients with uncomplicated influenza have found that timely treatment can reduce the duration of influenza symptoms and fever in pediatric populations.^122–126  Observational studies in pediatric and adult populations suggest that antiviral agents are safe and could reduce the risk of certain influenza complications, including hospitalization and death.^127–131  Potential limitations of the trials conducted to date in children include the study size (the number of events might not be sufficient to assess specific outcomes in small studies), variations in the case definition of influenza illness (clinically diagnosed versus laboratory confirmed), time of treatment administration in relation to the onset of illness, and inclusion of children of varying ages and underlying health conditions. Several studies also suggest that treatment of index patients with influenza reduces transmission to household contacts to some extent, but the magnitude of the effect is inconsistent across published reports.¹³²  The totality of available evidence supports the treatment of children with influenza.

A Cochrane review of 6 RCTs involving treatment of 2356 children with clinically diagnosed influenza, of whom 1255 had laboratory-confirmed influenza, showed that in children with laboratory-confirmed influenza, oral oseltamivir and inhaled zanamivir reduced median duration of illness by 36 hours (26%; P <.001) and 1.3 days (24%, P <.001), respectively.¹²⁶  Among the studies reviewed, 1 trial of oseltamivir in children with asthma who had laboratory-confirmed influenza showed only a nonsignificant reduction in illness duration (10.4 hours; 8%; P = .542). Oseltamivir significantly reduced acute otitis media in children 1 through 5 years of age with laboratory-confirmed influenza (risk difference [RD]: −0.14; 95% CI: −0.24 to −0.04).¹²⁶  Another Cochrane review of RCTs in adults and children, which included 20 oseltamivir (9623 participants) and 26 zanamivir trials (14 628 participants),¹²³  found no effect of oseltamivir in reducing the duration of illness in asthmatic children, but in otherwise healthy children, there was a reduction by a mean difference of 29 hours (95% CI: 12 hours to 47 hours; P = .001). No significant effect was observed with zanamivir. Regarding complications, this review did not find a significant effect of NAIs on reducing hospitalizations, pneumonia, bronchitis, otitis media, or sinusitis in children.¹²⁶  More recently, a meta-analysis of 5 new RCTs that included 1598 children with laboratory-confirmed influenza showed that treatment with oseltamivir significantly reduced the duration of illness in this population by 17.6 hours (95% CI: −34.7 hours to −0.62 hours).¹²⁴  When children with asthma were excluded, this difference was larger (−29.9 hours; 95% CI: −53.9 hours to −5.8 hours). The risk of otitis media was 34% lower in this group as well. Similarly, a meta-analysis conducted by Tejada et al showed a statistically significant reduction in the risk of acute otitis media occurrence among treated children over placebo recipients (odds ratio [OR]: 0.48; 95% CI: 0.30 to 0.77).¹³¹  Overall, efficacy outcomes are best demonstrated in patients with laboratory-confirmed influenza. All these studies confirmed vomiting as an occasional adverse effect of oseltamivir.

There are no prospective, fully enrolled, completed RCTs of antiviral agents versus placebo for treatment of influenza in hospitalized children or pediatric patients with comorbidities, and prospectively collected data to determine the role of antiviral agents in treating severe influenza are limited. One RCT of oseltamivir treatment of influenza in hospitalized children in El Salvador and Panama that suggested clinical benefit, but no statistically significant findings were reported, because only 21% of the target sample size was enrolled and therefore, the study was substantially underpowered.¹³³  Nevertheless, on the basis of information obtained from retrospective observational studies and meta-analyses conducted to date in both adults and children, most experts support the use of antiviral medications as soon as possible to treat pediatric patients with severe influenza, including hospitalized patients.^{125–130,133}  In a retrospective study of 784 pediatric ICU admissions from 2009 to 2012, the estimated risk of death was reduced in 653 NAI-treated cases (OR: 0.36; 95% CI: 0.16 to 0.83).¹³⁴  In a retrospective analysis of data from the US Influenza Hospitalization Surveillance Network, administration of antiviral agents ≤2 days after illness onset was associated with shorter lengths of stay in children admitted to the ICU (adjusted hazard ratio: 1.46; P = .007) and in children with underlying medical conditions not admitted to the ICU (adjusted hazard ratio: 1.37; P = .02). In the relatively small number of patients studied, antiviral treatment ≥3 days after illness onset had no significant effect in either cohort.¹³⁵ 

No additional benefit exists for double-dose NAI therapy on reduction of mortality or viral clearance, compared with standard-dose therapy, on the basis of a recent systematic review and meta-analysis of 10 published studies¹³⁶  (4 RCT and 6 observational studies) involving 20 947 adult and pediatric patients.

The AAP and the CDC, Infectious Diseases Society of America,¹¹³  and Pediatric Infectious Diseases Society recommend treatment with oseltamivir for children with serious, complicated, or progressive disease presumptively or definitively caused by influenza, irrespective of influenza vaccination status (the circulating strains may not be well matched with vaccine strains) or whether illness began >48 hours before presentation. Earlier treatment provides better clinical responses, but treatment after 48 hours of symptoms in adults and children with moderate to severe disease or with progressive disease has been shown to provide some benefit and should be offered.^134,137,138  Additionally, the AAP recommends treatment of children at risk for severe complications of influenza, regardless of duration of symptoms. Children younger than 2 years are at an increased risk of hospitalization and complications attributable to influenza. The FDA has approved oseltamivir for treatment of children as young as 2 weeks of age. Given preliminary pharmacokinetic data and limited safety data, the CDC and AAP support the use of oseltamivir to treat influenza in both term and preterm infants from birth, because benefits of therapy of neonatal influenza are likely to outweigh possible risks of treatment. Otherwise healthy children who have suspected influenza with an uncomplicated presentation should be considered for antiviral medication, particularly if they are in contact with other children who either are younger than 6 months (as they are not able to receive influenza vaccine) or have high-risk conditions, including age <5 years) that predispose them to complications of influenza, when influenza viruses are known to be circulating in the community. Antiviral treatment should be started as soon as possible after illness onset and should not be delayed while waiting for a definitive influenza test result, because early therapy provides the best outcomes. Algorithms for interpreting positive and negative influenza tests are available (https://www.cdc.gov/flu/professionals/diagnosis/algorithm- results-circulating.htm). The balance between benefits and harms should be considered when making decisions about the use of NAIs for either treatment or chemoprophylaxis of influenza. The cost of antiviral therapy may be a barrier to treatment of some families.

Oseltamivir is available in capsule and oral suspension formulations. The available capsule doses are 30 mg, 45 mg, and 75 mg, and the commercially manufactured liquid formulation has a concentration of 6 mg/mL in a 60 mL bottle. If the commercially manufactured oral suspension is not available, the capsule may be opened and the contents mixed with simple syrup or Ora-Sweet SF (sugar free) by retail pharmacies to a final concentration of 6 mg/mL.

In adverse event data collected systematically in prospective trials, vomiting was the only adverse effect reported more often with oseltamivir compared with placebo when studied in children 1 through 12 years of age (ie, 15% of treated children versus 9% receiving placebo). Diarrhea was reported in clinical trials of oseltamivir in 7% of treated children <1 year of age. Following reports from Japan of oseltamivir-attributable neuropsychiatric adverse effects, a review of controlled clinical trial data and ongoing surveillance has failed to establish a link between this drug and neurologic or psychiatric events.^139,140  Neurologic and neuropsychiatric complications including abnormal behavior occur in children with influenza in the absence of exposure to oseltamivir.¹⁴¹ 

Despite the growing body of evidence supporting antiviral treatment of children hospitalized with confirmed or suspected influenza and expert guidance recommending antiviral use, few data exist on adherence to these recommendations. In a study of 2299 hospitalized children with acute respiratory illness during the 2015 to 2016 influenza season, only 51% were tested for influenza. Fifty-two percent (61 of 117) of those who tested positive and 6% of those with a negative or unknown test (66 of 1066) were treated with antiviral agents.¹⁴²  In multivariable analyses, neuromuscular disease (aOR: 1.86; 95% CI: 1.04 to 3.31) and immunocompromised state (aOR: 2.63; 95% CI: 1.38 to 4.99) were positively associated with antiviral treatment, whereas duration of illness (aOR: 0.92; 95% CI: 0.84 to 0.99) and chronic lung disease (aOR: 0.60; 95% CI: 0.38 to 0.95) were negatively associated with antiviral treatment. Similarly, antiviral medications were underused in children hospitalized for influenza in Canadian pediatric hospitals over 9 seasons (2010 to 2011 through 2018 to 2019).¹⁴³  Only 41.3% were prescribed antiviral agents, even though antiviral use increased over the study period from 19.9% in the 2010 to 2011 season to 59.6% in 2018 to 2019 (P for trend = 0.001). Children with ≥1 chronic health condition were more likely to receive antiviral agents (52.7% vs 36.7%; P <.001); cancer was the condition most strongly associated with therapy (aOR: 4.81; 95% CI: 3.61 to 6.40) in multivariable logistic regression. Multifactorial interventions are urgently needed to increase adherence to antiviral treatment guidelines for children hospitalized with influenza.

Antiviral medications are important adjuncts to influenza vaccination for control and prevention of influenza disease in children who are at least 3 months of age. Randomized placebo-controlled studies showed that oral oseltamivir and inhaled zanamivir were efficacious when administered as chemoprophylaxis to household contacts after a family member had laboratory-confirmed influenza.¹¹³  The efficacy of baloxavir was demonstrated in a randomized, placebo-controlled trial in Japan conducted during the 2018–2019 season. One percent of household members 12 years and older treated with a single dose of baloxavir within 48 hours of exposure to a symptomatic household contact with influenza developed influenza compared with 13% in the placebo-treated group (aRR: 0.10; 95% CI: 0.04 to 0.28).¹¹⁹  For additional context, 73% started baloxavir within 24 hours of the index case’s symptom onset, an exercise that would be difficult to replicate in practice in the United States. There are no data on IV peramivir for chemoprophylaxis.

Decisions on whether to administer antiviral chemoprophylaxis should include consideration of the exposed person’s risk of influenza complications, vaccination status, type and duration of contact, time since exposure, recommendations from local or public health authorities, and clinical judgment. Optimally, postexposure chemoprophylaxis should only be used when antiviral agents can be started within 48 hours of exposure; the lower once-daily dosing for chemoprophylaxis with oral oseltamivir or inhaled zanamivir should not be used for treatment of children symptomatic with influenza.¹¹³  Early, full treatment dosing (rather than once daily chemoprophylaxis dosing) should be used in high-risk symptomatic patients without waiting for laboratory confirmation.

Toxicities may be associated with antiviral agents, and indiscriminate use might limit availability. Pediatricians should inform recipients of antiviral chemoprophylaxis that risk of influenza is lowered, but not eliminated, while taking the medication, and susceptibility to influenza returns when medication is discontinued. Chemoprophylaxis is not a substitute for vaccination and among some high-risk people, both vaccination with IIV and antiviral chemoprophylaxis may be considered.¹¹³  The effectiveness of LAIV but not IIV or RIV will be decreased for children receiving oseltamivir or other influenza antiviral agents.¹¹³  Updates will be available at www.aapredbook.org/flu and www.cdc.gov/flu/professionals/antivirals/index.htm.

Influenza diagnostic tests vary by method, availability, processing time, sensitivity, and cost (Table 3). Positive and negative predictive values of influenza test results are influenced by the level of influenza activity in the population being tested, whether the influenza virus is actively replicating in the person, characteristics of a test compared with a gold standard, pretest probability, proper collection and transport of specimens, and proper test procedures. Testing should be performed when timely results will be available to influence clinical management or infection control measures. Although decisions on treatment and infection control can be made on the basis of positive rapid test results, particularly when influenza viruses are known to be circulating, negative results should not always be used in a similar fashion because of the suboptimal sensitivity and potential for false-negative results. An updated list of rapid influenza diagnostic tests (RIDTs) is available at https://www.cdc.gov/flu/professionals/diagnosis/table-ridt.html. Some available RIDTs detect SARS-CoV-2 as well as influenza A and B. Positive results of RIDTs are helpful because they may reduce additional testing to identify the cause of the child’s influenza-like illness and promote appropriate antimicrobial stewardship. Available FDA-approved rapid molecular assays based on nucleic acid detection are highly sensitive and specific diagnostic tests that can provide rapid results. An updated list of these tests is available at https://www.cdc.gov/flu/professionals/diagnosis/table-nucleic-acid-detection.html. Multiplex assays that allow for the simultaneous detection of influenza viruses and SARS-CoV-2 or influenza viruses, SARS-CoV-2, and respiratory syncytial virus are available. These assays can be particularly useful when these viruses are cocirculating and because signs and symptoms of these viruses may be similar, clinical differentiation is difficult and different treatment strategies are recommended. A current list of authorized tests is available at https://www.cdc.gov/flu/professionals/diagnosis/table- flu-covid19-detection.html. Molecular assays are preferred in hospitalized patients because they are more sensitive compared with antigen detection. Early detection, prompt antiviral treatment, and infection-control interventions can lead to improved individual patient outcomes and allow for effective cohorting and disease containment.

Resistance to any antiviral drug can emerge, necessitating continuous population-based assessment by the CDC. During the 2020 to 2021 season, few influenza viruses were assessed for antiviral drug susceptibility, and no evidence of reduced inhibition or reduced susceptibility was detected. During the 2021 to 2022 season (an extended season), through the typical end of the seasonal surveillance period (week 20 which correlates to late May each year), among tested viruses, the prevalence of reduced inhibition or reduced susceptibility was extremely low. One of 1367 influenza A(H3N2) viruses tested had reduced susceptibility to baloxavir (https://www.cdc.gov/flu/weekly/weeklyarchives2021-2022/week20.htm).

Following treatment with baloxavir, emergence of viruses with molecular markers associated with reduced susceptibility to baloxavir has been observed in clinical trials in immunocompetent children and adults, with higher detection among baloxavir-treated pediatric patients aged <12 years compared with adults.^144–148  Historically, decreased susceptibility to baloxavir has been reported in Japan, where its use has been more common,^{144–146,149,150}  and surveillance for resistance among circulating influenza viruses is ongoing in Japan and the United States.^151–153  Globally, detection of viruses with reduced susceptibility to baloxavir or carrying amino acid substitutions associated with reduced susceptibility remain low (0.5% during the 2018 to 2019 season and 0.1% during the 2019 to 2020 season).¹⁵⁴  In contrast, high levels of resistance to amantadine and rimantadine persist among the influenza A viruses currently circulating; neither drug is effective against influenza B viruses. Adamantane medications are not recommended for use against influenza unless resistance patterns change.¹¹³ 

If a newly emergent oseltamivir- or peramivir-resistant virus is a concern, recommendations for alternative treatment will be available from the AAP and CDC. Resistance characteristics can change for an individual patient over the duration of a treatment course, especially in those who are severely immunocompromised. Up-to-date information on current recommendations and therapeutic options can be found on the AAP Web site (www.aap.org or www.aapredbook.org/flu), through state-specific AAP chapter websites, or on the CDC Web site (www.cdc.gov/flu/).

Continued evaluation of the safety, immunogenicity, and effectiveness of influenza vaccines, especially for at-risk and diverse populations, is important. The duration of protection, potential role of previous influenza vaccination on overall vaccine effectiveness, and vaccine effectiveness by vaccine formulation, virus strain, timing of vaccination, and subject age and health status, in preventing outpatient medical visits, hospitalizations, and deaths continue to be evaluated.

Development efforts continue for universal influenza vaccines that induce broader protection and eliminate the need for annual vaccination. The success of messenger RNA (mRNA) and other novel technologies used in the development of COVID-19 vaccines may accelerate the prospects of broad influenza vaccines. Understanding the establishment of immunity against influenza in early life and developing a safe, immunogenic vaccine for infants younger than 6 months are essential. Studies on the effectiveness and safety of influenza vaccines containing adjuvants that enhance immune responses to influenza vaccines or that use novel routes of administration are needed. Efforts to improve the vaccine development process to allow for a shorter interval between identification of vaccine strains and vaccine production continue.

Systematic health services research is needed to examine influenza vaccination coverage, factors associated with undervaccination, and interventions to increase uptake in diverse populations. National data from 2019 found that 25.8% of parents were hesitant about the influenza vaccine.¹⁵⁵  Moreover, children of parents who were hesitant about childhood vaccines had 25.6% lower influenza vaccination coverage in the 2018 to 2019 season compared with children of parents not reporting hesitancy.¹⁵⁶  Vaccine hesitancy has remained a major public health threat during the COVID-19 pandemic. Future studies should aim to improve our understanding of influenza vaccine hesitancy and identify effective strategies to address parental concerns, foster greater vaccine confidence, and increase influenza vaccine acceptance. Engagement of key stakeholder groups in this work is crucial, including patients and families, health care professionals, practices, and systems, public health officials, and community leaders. Enhanced collaboration may facilitate more equitable influenza vaccine supply and delivery and more effective community outreach, particularly to vulnerable populations. Novel approaches for reducing barriers to accessing preventive care services may also help to reduce disparities in influenza vaccination coverage. Lastly, ongoing efforts should include broader implementation and evaluation of mandatory HCP vaccination programs in both inpatient and outpatient settings.

New antiviral drugs are in various development phases, given the need to improve options for the treatment and chemoprophylaxis of influenza. Additionally, with limited data on the use of antiviral agents in hospitalized children and in children with underlying medical conditions, prospective clinical trials to inform optimal timing and efficacy of antiviral treatment in these populations are warranted, particularly as new antiviral agents or new indications for existing antiviral agents become available. Barriers to treatment of children at high-risk for complications, especially hospitalized patients, must be explored.

Pediatricians can remain informed of advances and other updates during the influenza season by following the CDC Influenza page (www.cdc/gov/flu) and the AAP Red Book Online Influenza News and Resource Page (www.aapredbook.org/flu).

• Sean T. O’Leary, MD, MPH, FAAP, Chairperson

• James D. Campbell, MD, MS, FAAP, Vice Chairperson

• Monica I. Ardura, DO, MSCS, FAAP

• Ritu Banerjee, MD, PhD, FAAP

• Kristina A. Bryant, MD, FAAP

• Mary T. Caserta, MD, FAAP

• Chandy C. John, MD, MS, FAAP

• Jeffrey S. Gerber, MD, PhD, FAAP

• Athena P. Kourtis, MD, PhD, MPH, FAAP

• Angela Myers, MD, MPH, FAAP

• Pia Pannaraj, MD, MPH, FAAP

• Adam J. Ratner, MD, MPH, FAAP

• José R. Romero, MD, FAAP

• Samir S. Shah, MD, MSCE, FAAP

• Kenneth M. Zangwill, MD, FAAP

• Yvonne A. Maldonado, MD, FAAP

• Annika M. Hofstetter, MD, PhD, MPH, FAAP

• Juan D. Chaparro, MD, MS, FAAP

• Jeremy J. Michel, MD, MHS, FAAP

• David W. Kimberlin, MD, FAAP – Red Book Editor

• Elizabeth D. Barnett MD, FAAP– Red Book Associate Editor

• Ruth Lynfield, MD, FAAP, Red Book Associate Editor

• Mark H. Sawyer, MD, FAAP – Red Book Associate Editor

• Henry H. Bernstein, DO, MHCM, FAAP – Red Book Online Associate Editor

• Karen M. Farizo, MD, US Food and Drug Administration

• Lisa M. Kafer, MD, FAAP, Committee on Practice Ambulatory Medicine

• David Kim, MD, HHS Office of Infectious Disease and HIV/AIDS Policy

• Eduardo López Medina, MD, MSc, Sociedad Latinoamericana de Infectologia Pediatrica

• Denee Moore, MD, FAAFP, American Academy of Family Physicians

• Lakshmi Panagiotakopoulos, MD, MPH, Centers for Disease Control and Prevention

• Laura Sauvé, MD, MPH, FAAP, FRCPS, Canadian Pediatric Society

• Jeffrey R. Starke, MD, FAAP, American Thoracic Society

• Jennifer Thompson, MD, American College of Obstetricians and Gynecologists

• Kay M. Tomashek, MD, MPH, DTM, National Institutes of Health

• Melinda Wharton, MD, MPH, Centers for Disease Control and Prevention

• Charles R. Woods, Jr, MD, MS, FAAP, Pediatric Infectious Diseases Society

Jennifer M. Frantz, MPH

The Committee on Infectious Diseases gratefully acknowledges Kristina A. Bryant, MD, FAAP, and Annika M. Hofstetter, MD, PhD, MPH, FAAP, for their leadership in drafting the policy statement and technical report; and Juan D. Chaparro, MD, MS, FAAP, and Jeremy J. Michel, MD, MHS, FAAP, for their significant contributions in providing input on the initial drafts on behalf of the AAP Partnership for Policy Initiative.

Lessin HR; Edwards KM; American Academy of Pediatrics, Committee on Practice and Ambulatory Medicine, Committee on Infectious Diseases. Immunizing parents and other close family contacts in the pediatric office setting. Pediatrics. 2012;129(1):e247

American Academy of Pediatrics, Committee on Infectious Diseases. Policy statement: Influenza immunization for all health care personnel: keep it mandatory. Pediatrics. 2015;136(4):809–818

American Academy of Pediatrics, Committee on Pediatric Emergency Medicine. Preparation for emergencies in the offices of pediatricians and pediatric primary care providers. Pediatrics. 2007;120(1):200–212. Reaffirmed June 2011.

American Academy of Pediatrics, Committee on Practice and Ambulatory Medicine, AAP Committee on Infectious Diseases, AAP Committee on State Government Affairs, AAP Council on School Health, AAP Section on Administration and Practice Management. Medical Versus Nonmedical Immunization Exemptions for Child Care and School Attendance. Pediatrics. 2016;138(3):e20162145

Edwards KM, Hackell JM; American Academy of Pediatrics, Committee on Infectious Diseases, Committee on Practice and Ambulatory Medicine. Countering vaccine hesitancy. Pediatrics. 2016;138(3):e20162146

American Academy of Pediatrics, Committee on Pediatric Emergency Medicine; American Academy of Pediatrics Committee on Medical Liability; Task Force on Terrorism. The pediatrician and disaster preparedness. Pediatrics. 2006;117(2):560–565. Reaffirmed September 2013

American Academy of Pediatrics. Influenza. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. Elk Grove Village, IL: American Academy of Pediatrics; 2018:476–489. Available at: http://aapredbook.aappublications.org/flu

AAP

American Academy of Pediatrics

ACIP

Advisory Committee on Immunization Practices

aOR

adjusted odds ratio

CDC

Centers for Disease Control and Prevention

CI

confidence interval

FDA

US Food and Drug Administration

HCP

health care personnel

IIV

inactivated influenza vaccine

IIV4

quadrivalent inactivated influenza vaccine

LAIV

live attenuated influenza vaccine

LAIV4

quadrivalent live attenuated influenza vaccine

NAI

neuraminidase inhibitor

RCT

randomized controlled trial

RIV

recombinant influenza vaccine

RIV4

quadrivalent recombinant influenza vaccine

VE

vaccine effectiveness